Glucagon-Like Peptide-1 Receptor Agonists and Risk for Depression in Older Adults With Type 2 Diabetes : A Target Trial Emulation Study.

IF 15.2 1区医学 Q1 MEDICINE, GENERAL & INTERNAL Annals of Internal Medicine Pub Date : 2025-03-01 Epub Date: 2025-02-25 DOI:10.7326/ANNALS-24-01347

Huilin Tang, Ying Lu, William T Donahoo, Sarah C Westen, Yong Chen, Jiang Bian, Jingchuan Guo

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Abstract

Background: Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential antidepressant effects, population studies yield inconsistent results.

Objective: To compare the risk for depression in older adults with type 2 diabetes (T2D) initiating treatment with GLP-1RAs versus sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is).

Design: Target trial emulation study.

Setting: U.S. National Medicare administrative data from January 2014 to December 2020.

Patients: Adults aged 66 years or older with T2D initiating treatment with a GLP-1RA were matched 1:1 on propensity score with those initiating treatment with either an SGLT2i or a DPP4i.

Measurements: The primary end point was incident depression. Cox proportional hazards regression models were used to estimate the hazard ratio (HR) with 95% CI within matched groups.

Results: A total of 14 665 matched pairs of older adults were included in the cohort for GLP-1RAs versus SGLT2is; the rate difference of depression between GLP-1RA users and SGLT2i users was 3.48 (95% CI, -0.81 to 7.78) per 1000 person-years, with an HR of 1.07 (CI, 0.98 to 1.18). In the cohort for GLP-1RAs versus DPP4is (13 711 matched pairs), the rate difference was -5.78 (CI, -10.49 to -1.07) per 1000 person-years, with an HR of 0.90 (CI, 0.82 to 0.98).

Limitation: Unmeasured confounders (such as hemoglobin A_1c levels and body mass index), outcome misclassification, and limited generalizability to all GLP-1RA users (for example, younger populations or those without T2D receiving the drug for obesity treatment).

Conclusion: Among older adults with T2D, the incidence of depression was relatively low. Use of GLP-1RAs was associated with a modestly lower risk for depression compared with use of DPP4is, but not SGLT2is.

Primary funding source: National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

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胰高血糖素样肽-1 受体激动剂与 2 型糖尿病老年患者的抑郁风险：目标试验模拟研究

背景：虽然胰高血糖素样肽-1受体激动剂（GLP-1RAs）显示出潜在的抗抑郁作用，但人群研究结果不一致。目的：比较GLP-1RAs与钠-葡萄糖共转运蛋白-2抑制剂（SGLT2is）或二肽基肽酶-4抑制剂（DPP4is）开始治疗的老年2型糖尿病（T2D）患者抑郁的风险。设计：目标试验仿真研究。数据设置：2014年1月至2020年12月的美国国家医疗保险行政数据。患者：66岁或以上的t2dm患者开始使用GLP-1RA治疗，与开始使用SGLT2i或DPP4i治疗的患者在倾向评分上1:1匹配。测量：主要终点为偶发抑郁。使用Cox比例风险回归模型估计匹配组内95% CI的风险比（HR）。结果：共有14665对匹配的老年人被纳入GLP-1RAs与SGLT2is的队列；GLP-1RA使用者和SGLT2i使用者的抑郁率差异为3.48 (95% CI, -0.81 ~ 7.78) / 1000人年，HR为1.07 （CI, 0.98 ~ 1.18）。在GLP-1RAs与DPP4is的队列中（13711对配对），每1000人年的比率差异为-5.78 (CI, -10.49至-1.07)，HR为0.90 （CI， 0.82至0.98）。局限性：未测量的混杂因素（如血红蛋白A1c水平和体重指数），结果错误分类，以及对所有GLP-1RA使用者的有限推广性（例如，年轻人群或接受肥胖治疗的无T2D人群）。结论：老年T2D患者抑郁发生率相对较低。与使用DPP4is相比，GLP-1RAs的使用与抑郁风险适度降低相关，但与SGLT2is无关。主要资金来源：美国国立卫生研究院糖尿病、消化和肾脏疾病研究所。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Internal Medicine 医学-医学：内科

CiteScore

23.90

自引率

1.80%

发文量

1136

审稿时长

3-8 weeks

期刊介绍： Established in 1927 by the American College of Physicians (ACP), Annals of Internal Medicine is the premier internal medicine journal. Annals of Internal Medicine’s mission is to promote excellence in medicine, enable physicians and other health care professionals to be well informed members of the medical community and society, advance standards in the conduct and reporting of medical research, and contribute to improving the health of people worldwide. To achieve this mission, the journal publishes a wide variety of original research, review articles, practice guidelines, and commentary relevant to clinical practice, health care delivery, public health, health care policy, medical education, ethics, and research methodology. In addition, the journal publishes personal narratives that convey the feeling and the art of medicine.